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Relaxant responses to calcium channel antagonists and potassium channel opener in human saphenous vein

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1 As shown in a parallel study the magnitude of depolarization induced in human saphenous vein by raising external potassium ([K+]e) falls markedly below the theoretical values predicted by the Goldman–Hodgkin–Katz equations. This anomaly prompted us to re-examine the relaxant actions of L-type (nifedipine) and T-type (mibefradil) Ca2+ channel antagonists, and relaxant and electrophysiological effects of the K+ channel opener, pinacidil, on saphenous veins contracted by the elevation of [K+]e.

2 Nifedipine produced concentration–dependent relaxations in tissues contracted at various high [K+]e. In tissues contracted with 20 m m [K+]e, the pIC50 for nifedipine was significantly (8.20 ± 0.05; n = 6; mean ± SEM; P < 0.05) greater than in tissues contracted with ≥40 m m [K+]e.

3 Tissues contracted with 20 m m [K+]e also relaxed in response to mibefradil (pIC50 = 6.1 ± 0.14) and pinacidil (pIC50 = 6.45 ± 0.08), the latter being almost completely reversed (93.4 ± 9.9%) by addition of glibenclamide (10  m).

4 The resting Em of smooth muscle cells of saphenous vein was −77.0 ± 0.7 mV (n = 52), and 20 m m [K+]e produced a modest but significant depolarization to −73.0 ± 0.7 mV (n = 52). Incubation with pinacidil plus 20 m m [K+]e resulted in a significant hyperpolarization of the Em to −82 ± 0.6 mV (n = 52).

5N-nitro- l-arginine methyl ester did not impede the relaxant responses of nifedipine, mibefradil or pinacidil.

6 In conclusion, the relaxant effects of nifedipine and pinacidil (i) occurred at an Em distinctly below the presumed threshold for the opening of the classic (CaV1.3α1) L-type Ca2+ channels, and (ii) did not depend on generation of nitric oxide.

Keywords: L-type and T-type channels; excitation–contraction coupling; human vascular smooth muscle; membrane potential; organic calcium channel antagonist; potassium channels

Document Type: Research Article


Affiliations: 1: Division of Basic Medical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St John's, NL, A1B 3V6 2: Discipline of Surgery, Health Care Corporation of St. John's, St John's, NL, Canada

Publication date: 2006-01-01

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